BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

ObjectiveBased on the quality evaluation experience of "it is better to have a fragrant and strong aroma" summarized by materia medica of past dynasties， the chemical components of Sojae Semen Nigrum（SSN） and Sojae Semen Praeparatum（SSP） were systematically compared and analyzed， and the main fermentation products in different fermentation time were quantitatively analyzed， so as to clarify the transformation law of internal components in the processing process and provide scientific basis for the modern quality control of SSP. MethodUltra performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used for the structural identification of the chemical constituents of SSN and SSP， and with the aid of Progenesis QI v2.3 software， the negative ion mode was employed for principal component analysis（PCA） pattern recognition， and the data were analyzed with the aid of orthogonal partial least squares-discriminant analysis（OPLS-DA） for two-dimensional data to obtain S-plot， and components with |P|>0.1 were selected as the differential constituents. The contents of isoflavonoids in SSP during fermentation was determined by UPLC， and the samples were taken every 8 h in the pre-fermentation period and every 2 d in the post-fermentation period， and the dynamic changes of isoflavonoid contents in different fermentation stages were analyzed. The contents of amino acids and nucleosides in SSP and SSN from different fermentation stages were quantitatively analyzed by phenyl isothiocyanate（PITC） pre-column derivatization and high performance liquid chromatography（HPLC） gradient elution， and the contribution of flavor substances to the "delicious" taste of SSP was discussed by taste intensity value（TAV）. ResultA total of 19 kinds of differential components were screened out， mainly soybean saponins and isoflavones， and their contents decreased significantly or even disappeared after fermentation. In the pre-fermentation process of SSP， glycoside bond hydrolysis mainly occurred， and isoflavone glycosides in SSN were degraded and converted into the corresponding aglycones， the content of flavor substances such as amino acids increased gradually. In the post-fermentation process， protein degradation mainly occurred， after 8 d of post-fermentation， the content of isoflavones was basically stable， while the total content of amino acids increased by 8-40 times on average. Different amino acids form the special flavor of SSP， such as the TAV of glutamate is always ahead of other flavor substances， and sweet substances such as alanine and valine have made relatively great contributions to SSP. ConclusionBased on the law of constituent transformation， combined with the traditional evaluation index of "fragrant and strong"， it is difficult to control the fermentation degree of SSP by the existing standards in the 2020 edition of Chinese Pharmacopoeia. It is suggested that description of the characteristics of SSP be refined and changed to "fragrant， delicious and slightly sweet"， and at the same time， the post-fermentation index compounds such as glutamic acid， alanine and valine should be added as the quality control indicators of SSP， so as to standardize the production process and improve the quality of SSP.

Gag-Pol protein is one of the important structural proteins of human immunodeficiency virus(HIV),comprising the basic scaffold proteins and functional enzymes required during the lifecycle of HIV.Currently,the inhibitors targeting different functional domains on Gag-Pol include capsid(CA)inhibitors,protease inhibitors,reverse transcriptase inhibitors,and integrase inhibitors.The CA inhibitors inhibit the maturation of CA or disrupt the assembly of CA,so as to affect the replication of HIV.The primary mechanism of protease inhibitors is to inhibit the protease from cleaving at the cleavage site CA-spacer peptide 1(SP1).The reverse transcriptase inhibitors block the reverse transcription process of HIV by mimicking the reverse transcription substrates.The integrase inhibitors impact the activity of integrase by targeting the zinc-finger structure at the active center of integrase.This article summarizes the inhibitors targeting HIV Gag-Pol protein and their mechanisms,and reviews the approved dosages and usages of approved patent drugs,so as to provide the references for the future clinical combination therapies and the development of new inhibitors targeting HIV Gag-Pol protein.

Intracerebral hemorrhage(ICH)is a nervous system disease that seriously endangers human health,with a very high rate of disability and fatality.Most survivors will leave behind varying degrees of neu-rological dysfunction.Therefore,early assessment of neurological function in the patients with cerebral hemor-rhage has an important clinical significance.Diffusion tensor imaging(DTI)is a nuclear magnetic resonance technique to noninvasively reconstruct the structure and path of nerve fiber bundles in vivo,which can be used to the condition evaluation and prognosis judgment after ICH,and has an important clinical significance for the evaluation of neurological dysfunction.This paper reviews the related value of DTI in the prognosis evaluation of the patients with ICH.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared

An in vitro blood-brain barrier (BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system. Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport. Induced-pluripotent stem cell (iPSC) technology provides reproducible cell resources for in vitro BBB modeling. Here, we generated a human in vitro BBB model by differentiating the human iPSC (hiPSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins (ZO-1, claudin-5, and occludin) and endothelial markers (von Willebrand factor and Ulex), as well as high trans-endothelial electrical resistance (TEER) (1560 Ω.cm ± 230 Ω.cm) and γ-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model (2970 Ω.cm to 4185 Ω.cm). RNAseq analysis confirmed the expression of key BBB-related genes in the hiPSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells, including P-glycoprotein (Pgp) and breast cancer resistant protein (BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds (R = 0.982 and R = 0.9973, respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

Objective: To summarize the experience of surgical treatment of 18 cases of severe aortic stenosis with ventricular septum hypertrophy. Methods: Clinical data of 18 patients with severe aortic stenosis admitted to the first affiliated hospital of zhengzhou university from January 2013 to December 2016 were collected. There were 7 males and 11 females. The mean age was (50.4±4.2) years old. All patients were diagnosed with severe stenosis of main artery valve by echocardiography before surgery, with mean aortic valve orifice area (0.57±0.11) cm^2, cardiac function (NYHA classification) grade Ⅱ in 4 patients, grade Ⅲ in 9 patients, and grade Ⅳ in 5 patients. There were 8 patients with mild aortic valve insufficiency, 4 patients with mild to moderate mitral valve insufficiency, 2 patients with moderate to severe aortic valve insufficiency, 3 patients with ascending aorta dilatation (ascending aorta inner diameter>4.5 cm), and 1 patient with atrial fibrillation. Interventricular septum thickness (15.82±2.04)mm, left ventricular posterior wall thickness (14.04±1.28)mm, ratio of interventricular septum thickness to left ventricular posterior wall thickness (IVS/LVPW) 1.12±0.91, inner diameter of left ventricular outflow tract (19.01±1.74)mm, cross-lobe differential pressure (102±8.40) mmHg (1 mmHg=0.133 kPa), left ventricular ejection fraction (LVEF) mean 0.49±0.05. Left ventricular end-diastolic diameter (LVEDD) (53.33±4.00) mm, left ventricular end-systolic diameter (LVESD) (27.11±1.99) mm, and left ventricular mass index (277.1±37.3) g/m². All patients underwent aortic valve replacement (AVR) and partial interventricular septum resection under general anesthesia and conventional extracorporeal circulation, 2 patients underwent mitral valve formation (artificial valve ring), 2 patients underwent ascending aorta formation, and 1 patient underwent ascending aorta wrapping. During the operation, the time of extracorporeal circulation, aortic occlusion, number of defibrillation during the operation, type of valve implantation and postoperative complications were recorded. Regular follow-up was conducted to analyze the changes of various indexes at different preoperative and postoperative time. Results: There was no death in the whole group. 2 patients were treated with temporary pacemakers. After drug treatment, sinus rhythm was restored on the 3rd and 6th day after surgery, and temporary pacemakers were removed. Echocardiography reexamination 1 week after the operation showed that all patients had a good artificial valve function and 2 patients had minor regurgitation of mitral valve. The difference in pressure across the valve, inner diameter of the left ventricular outflow tract, cardiac function classification, ventricular septum thickness, valve orifice area, and left ventricular mass index were significantly improved compared with the preoperative level (P<0.05). LVEF, LVEDD, and LVESD were compared with the preoperative level (P<0.05). After 6 months of follow-up, the difference in LVEF and LVEDD was statistically significant compared with the preoperative level (P<0.05). Conclusion Severe aortic stenosis combined with ventricular septum hypertrophy and partial ventricular septal muscle resection is a simple additional procedure in the AVR process, which does not increase the surgical risk and has a significant effect, and is conducive to postoperative left ventricular function recovery.

Objective To investigate the appropriate age of primary and secondary school students for cardiopulmonary resuscitation (CPR) training.Methods A total of 437 students aged 9-15 years at 3 to 6 grade in the primary schools or 1 to 2 grade in the secondary schools were selected from 2 Yuyao primary and secondary schools by stratified random sampling between March 2017 and January 2018.The numbers of students with the age of 9,10,11,12,13,14 and 15 y were 61,62,66,64,63,63 and 58,respectively.All students received chest compression training provided by Yuyao emergency department People's Hospital according to the 2015 Cardiopulmonary Resuscitation Guidelines.The training included 30 min theoretic teaching and 6 min practice in the simulator.The quality of chest compression performed by students was assessed;the depth,rate,position and retention of chest compression were recorded.Results The mean depth of chest compression in the students aged 9-15 years was 3.8,4.1,4.6,5.1,5.2,5.6 and 5.6 cm,respectively;the accuracy rate was 24.6％(14/61),25.8％ (16/62),50.2％ (33/66),70.5％ (45/64),79.4％(50/63),88.9％(56/63) and 91.4(53/58),respectively.Compared with the students aged 9-11 years,the mean depth of chest compression was significantly increased and accuracy rate was significantly improved in the students aged 12-15 years (Compared with 9-y students,t=-8.936,-9.502,-10.640 and-11.370;x2=35.019,47.599,63.013 and 65.671;compared with 10-y students,t=-6.927,-8.179,-10.70 and-11.047;x2=24.977,35.967,50.916 and 52.727;compared with 1 1-y students,t=-3.095,-4.177,-6.785 and-6.995;x2=5.586,12.114,22.786 and 24.870;all P＜0.05).The mean rate of chest compression was 110-116/min and its accuracy rate was 86.4％-95.2％;the accuracy rate of chest compression position was 90.9％-96.8％ in all students,there were no significant differences among the 7 groups.The mean retention rate of chest compression in the 7 groups was 81.3％(122/150),67.3％(101/150),64.7％ (94/150),48.0％(72/150),48.7％(73/150),33.3％(50/150) and 27.3％(41/150),respectively.Compared with the students aged 9-11 years,the mean retention rate of chest compression was significantly decreased in the students aged 12-15 years (compared with the 9-y students,x2=36.472,35.179,70.64 and 119.92;compared with 10-y students,x2=11.483,10.728,34.682 and 72.150;compared with 11-y students,x2=6.528,5.927,25.855 and 59.11;all P＜0.05).Correlation analysis showed that the depth (r=0.96,0.89,0.91 and 0.86;P＜0.01) and retention rate (r=-0.99,-0.90,-0.93 and-0.86;all P＜0.01) of chest compression were significantly associated with the age,body weight,height and body mass index of students.Conclusion The students with an age of 12 years or more are able to effectively perform chest compression;thus,12 years and above might be the appropriate age for CPR training.